Influence of Antibiotic Use on the Effectiveness and Safety of Immune Checkpoint Inhibitors

Abstract

It has been reported that antibiotic (ATB) use changes the gut microbiome and alters the outcome of treatment with immune checkpoint inhibitors (ICIs). In this retrospective, single-center cohort study, we investigated the effects of concurrent use of PD-1 inhibitors and medications known to modify the gut microbiome including ATBs on the clinical benefit or safety of PD-1 inhibitors across types of cancer in Japanese patients. In total, 143 patients were analyzed: 53 patients received systemic ATBs within 2 months before or 1 month after the first dose of PD-1 inhibitors (the ATB group); the remaining patients comprised the non-ATB group. There was a significantly higher proportion of patients under 65 years of age in the ATB group. Progression-free survival (PFS) in the ATB group was significantly shorter than that in the non-ATB group across types of cancer (HR = 1.82). It is suggested that anti-anaerobic ATBs may be associated with worse PFS. The higher disease control rate was associated with the non-ATB group compared with the ATB group. A multivariate Cox proportional hazard model constructed with PFS showed that the impact of ATBs remained significant for PFS and probiotic use was detected as another independent factor involved in shorter PFS. There were similar frequencies and conditions between the two groups in the incidence of adverse events of Grade 3 or above, and laboratory data. Our results suggest that the use of ATBs may negatively affect the anticancer treatment outcomes of Japanese patients who are administered PD-1 inhibitors.